title: Protein kinase Czeta represses the interleukin-6 promoter and impairs tumorigenesis in vivo.
abstract: Gene alterations in tumor cells that confer the ability to grow under nutrient- and mitogen-deficient conditions constitute a competitive advantage that leads to more-aggressive forms of cancer. The atypical protein kinase C (PKC) isoform, PKCzeta, has been shown to interact with the signaling adapter p62, which is important for Ras-induced lung carcinogenesis. Here we show that PKCzeta-deficient mice display increased Ras-induced lung carcinogenesis, suggesting a new role for this kinase as a tumor suppressor in vivo. We also show that Ras-transformed PKCzeta-deficient lungs and embryo fibroblasts produced more interleukin-6 (IL-6), which we demonstrate here plays an essential role in the ability of Ras-transformed cells to grow under nutrient-deprived conditions in vitro and in a mouse xenograft system in vivo. We also show that PKCzeta represses histone acetylation at the C/EBPbeta element in the IL-6 promoter. Therefore, PKCzeta, by controlling the production of IL-6, is a critical signaling molecule in tumorigenesis.
authors.affiliation: Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, 3125 Eden Ave., Cincinnati, OH 45267, USA.
authors.forename: Anita S
authors.initials: AS
authors.lastname: Galvez
authors.forename: Angeles
authors.initials: A
authors.lastname: Duran
authors.forename: Juan F
authors.initials: JF
authors.lastname: Linares
authors.forename: Peterson
authors.initials: P
authors.lastname: Pathrose
authors.forename: Elias A
authors.initials: EA
authors.lastname: Castilla
authors.forename: Shadi
authors.initials: S
authors.lastname: Abu-Baker
authors.forename: Michael
authors.initials: M
authors.lastname: Leitges
authors.forename: Maria T
authors.initials: MT
authors.lastname: Diaz-Meco
authors.forename: Jorge
authors.initials: J
authors.lastname: Moscat
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011493:Protein Kinase C / Q000172:deficiency / Q000378:metabolism*; D044967:Serum; D014158:Transcription, Genetic; D000099221:Protein Kinase C zeta
chemical_list: D015850:Interleukin-6; D016328:NF-kappa B; D011493:Protein Kinase C; D000099221:Protein Kinase C zeta